Plasma miRNA profiling in patients with hepetocellular carcinoma and liver cirrhosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE294055 | GEO | 2025/06/12
REPOSITORIES: GEO
Similar Datasets
Project description:Exosomal microRNAs have recently been studied as potential diagnostic marker for various malignancies, including hepatocellular carcinoma (HCC). The aim of this study was to investigate serum exosomal microRNA profiles as HCC diagnostic marker. Transmission electron microscopy and western blot were used to identify serum exosomes. Deep sequencing was performed to screen differentially expressed microRNAs between HCC (n=5) and liver cirrhosis (LC, n=5) group. Three upregulated and two downregulated microRNAs were selected for qPCR analysis. The levels of selected microRNAs were normalized to Caenorhabditis elegans miR-39 microRNA mimics. Serum exosomal level of miR-122, miR-148a, and miR-1246 were further analyzed and significantly higher in HCC than LC and normal control (NC) group (P<0.001), but not different from chronic hepatitis group(p>0.05). The receiver operating characteristic curve was used to evaluate diagnostic perfromance of candidate microRNAs. Area under the curve (AUC) of miR-148a was 0.891 [95 % confidence interval (CI), 0.809-0.947] in discriminating HCC from LC, remarkably higher than alpha fetoprotein (AFP) (AUC: 0.712, 95 % CI: 0.607-0.803). Binary logistic regression was adpoted to establish the diagnostic model for discriminating HCC from LC. And the combination of miR-122, miR-148a and AFP increased the AUC to 0.931 (95% CI, 0.857-0.973), which can also be applied for distinguishing early HCC from LC. miR-122 was the best for differentiating HCC from NC (AUC: 0.990, 95% CI, 0.945-1.000). These data suggests that serum exosomal microRNAs signature or their combination with traditional biomarker may be used as a suitable peripheral screening tool for HCC.
2018-10-01 | GSE104251 | GEO
Project description:Hepatocellular carcinoma (HCC) is one of the leading cause of cancer-related mortality worldwide. Liver cirrhosis is well-established risk factor of HCC development, although prevention of HCC in cirrhosis patients is challenging. By utilizing bioinformatic compound screening based on a clinical HCC-risk-predicitve gene signature, we identified captopril as a potential HCC chemoprevention agent. We tested the drug in rats with diethylnitrosamine (DEN)-induced cirrhosis and HCC, and confirmed its HCC-preventive effect.
2022-08-02 | GSE157919 | GEO
Project description:Gene-expression profiles of hepatitis C-related, early-stage liver cirrhosis Background & Aims: Liver cirrhosis affects 1%M-bM-^HM-^R2% of population and is the major risk factor of hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the US. Non-invasive methods have been developed to identify patients with asymptomatic, early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients newly diagnosed with cirrhosis but without HCC. Methods: We performed gene expression profile analysis of formalin-fixed needle biopsies from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. Results: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P=.004), progression to advanced cirrhosis (P<.001), and development of HCC (P=.009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidences of HCC were 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. Conclusions: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent their development of HCC. 216 liver biopsy specimens
2013-01-22 | E-GEOD-15654 | biostudies-arrayexpress
Project description:BACKGROUND & AIMS: Cirrhosis affects 1% to 2% of the world population and is the major risk factor for hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the United States. Noninvasive methods have been developed to identify patients with asymptomatic early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients with newly diagnosed cirrhosis but without HCC. METHODS: We performed gene expression profile analysis of formalin-fixed needle biopsy specimens from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed up for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. RESULTS: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P = .004), progression to advanced cirrhosis (P < .001), and development of HCC (P = .009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidence of HCC was 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. CONCLUSIONS: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent the development of HCC.
2013-01-22 | GSE15654 | GEO
Project description:A quantitative label-free proteome analysis was performed using plasma samples from 22 hepatitis-C virus (HCV)-induced liver cirrhosis patients, 16 HCV-positive hepatocellular carcinoma patients with underlying cirrhosis and 18 healthy controls. Plasma microparticles (PMPS) were isolated using ultracentrifugation and analyzed via label-free LC-MS/MS. A quantitative label-free proteome analysis was performed using plasma samples from 22 hepatitis-C virus (HCV)-induced liver cirrhosis patients, 16 HCV-positive hepatocellular carcinoma patients with underlying cirrhosis and 18 healthy controls. Plasma microparticles (PMPS) were isolated using ultracentrifugation and analyzed via label-free LC-MS/MS.
2017-06-21 | PXD005777 | Pride
Project description:Biomarker studies for early stage or preclinical hepatocellular carcinomas (HCC) are hindered by the difficulties of obtaining samples from asymptomatic individuals. We established animal models using irradiated mice to investigate circulating miRNA as non-invasive markers for detection of early stage HCC. We hypothesized that certain miRNAs that play pivotal roles in molecular pathways are conserved across species and identification of these miRNAs will facilitate studying human markers in mice. To test the hypothesis, we performed weighted gene co-expression analysis by integrating circulating miRNA and tumor gene expression profiles from individual mice and discovered hub miRNAs in highly correlated expression modules. We validated the hub miRNAs using F2 hybrid mice derived from radiogenic HCC susceptible and resistant founders and identified 38 circulating miRNA markers associated with radiation-induced HCC. Through literacy search, we selected 10 human HCC-associated circulating miRNAs that had been validated in multiple independent patient cohorts. Nine of the 10 human markers overlapped with the mouse hub miRNAs, indicating the feasibility of using mouse model to study human circulating HCC markers. Using serially collected plasma samples from irradiated mice, we studied the kinetics of circulating miRNAs. We found that the mouse plasma levels of 4 human circulating markers, miR-122-5p, miR-100-5p, miR-34a-5p and miR-365-3p increased linearly as the time approaching towards HCC detection, indicating the correlations of the 4 miRNAs with oncogenic progression. Estimation of change points in the kinetics of the 4 circulating miRNAs suggested the changes started months before HCC detection, ranging from 17.5 to 6.8 months. Our data demonstrated that the 4 circulating miRNAs were sensitive biomarkers potentially valuable for the screening of early stage HCC.
2022-07-06 | GSE196193 | GEO
Project description:Background: Of Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), 85%-90% of cases develop from liver cirrhosis, and circular RNAs (circRNAs) have important roles in this process; however, differences in serum circRNA expression profiles between patients with HBV-related cirrhosis and those with HCC have not been studied. Methods: Serum RNA was extracted from patients with HCC and cirrhosis (n = 5 per group) and used for microarray analysis of circRNA expression profiles. Bioinformatics analyses, including clustering, differential expression, and construction of a ceRNA network, were performed. Quantitative real-time reverse transcription PCR validation analysis was conducted using samples from patients with HBV-related cirrhosis (n = 88) and HCC (n = 73). Further, statistical analyses were used to analyze the potential function and value of selected circRNAs with expression differing between the HBV-related cirrhosis and HCC groups. Results: Cluster analysis revealed 8 up-regulated and 80 down-regulated circRNAs. Further, qRT-PCR analysis showed that circRNA_0000367 expression was consistent with that detected by microarray experiments, with significantly lower levels in patients with HBV-related HCC than those with HBV-related cirrhosis. CircRNA_0000367 expression levels were also significantly lower in patients with drug-resistant HBV and those with HBV-related cirrhosis with Model for End-Stage Liver Disease score < 10. Further, circRNA_00000367 expression levels were lower in patients with HBV-related cirrhosis who progressed to HCC. Analysis of the lncRNA-miRNA-mRNA ceRNA network identified 39 miRNAs and 24 mRNAs involved in circRNA_00000367 networks; these target genes were involved in various biological processes and signaling pathways. Conclusion: Serum cicrRNA_0000367 is a potential HCC biomarker in patients with HBV-related cirrhosis, where down-regulation of cicrRNA_0000367 in HBV-related cirrhosis may be associated with progression to HCC.
2025-02-10 | E-MTAB-12717 | biostudies-arrayexpress
Project description:The aim of this study is to compare post-hepatitis C virus (HCV) and post-alcoholism cirrhosis gene expression profiling. By transcriptome analysis with a cDNA array virtually covering every transcript in liver, we compared transcript levels in alcoholic- , HCV-cirrhosis and control liver. A stringent selection identified a list of 70 transcripts which completely separated the 3 groups of patients (7 HCV-cirrhosis, 7 alcoholic cirrhosis and 8 control livers). In contrast, in an hepatocellular carcinoma (HCC) context, comparison of 10 HCV-cirrhosis, 10 alcoholic cirrhosis and the 8 control livers failed to identify such transcripts. We report that dysregulations at the transcriptional level do exist in HCC-free cirrhosis, are transiently observed prior to detectable HCC. Keywords: etiology-dependent and HCC-dependent analysis
2008-02-01 | GSE10356 | GEO
Project description:Cirrhosis, advanced liver disease, affects 2-5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2 years. Among the patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care, reduce morbidity and mortality. This is important to preferentially direct them towards specialty care which cannot be provided to all patients with cirrhosis. We used discovery Top-down Proteomics (TDP) to detect differentially expressed proteoforms (DEPs) in the plasma of patients with cirrhosis with the goal to identify candidate biomarkers of disease progression. 663 DEPs were identified across three stages of cirrhosis (compensated, compensated with portal hypertension, and decompensated), of which 115 derived from proteins enriched in the liver at a transcriptional level and discriminated the progressive stages of cirrhosis. Enrichment analyses demonstrated DEPs are involved in numerous metabolic, oxidative, immunological, and hematological processes known to be impacted by cirrhosis progression. We have preliminarily defined the plasma proteoform signatures of cirrhosis patients, setting the stage for ongoing discovery and validation of biomarkers for early diagnosis, risk stratification, and disease monitoring.
2024-03-13 | MSV000094311 | MassIVE
Project description:Plasma miRNA profiling in patients with hepetocellular carcinoma and liver cirrhosis
| PRJNA1247971 | ENA